Open AccessIntegrative analysis of hub genes and key pathway in two subtypes of diffuse large B‐cell lymphoma by bioinformatics and basic experiments
Author(s) -
Li Qian,
Meng Ye,
Hu Linhui,
Charwudzi Alice,
Zhu Weiwei,
Zhai Zhimin
Publication year - 2021
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23978
Subject(s) - kegg , wnt signaling pathway , biology , gene , computational biology , diffuse large b cell lymphoma , cell cycle , gene expression profiling , biological pathway , gene expression , genetics , cancer research , transcriptome , lymphoma , bioinformatics , immunology
Background The germinal center B‐cell (GCB) and activated B‐cell (ABC) subtypes of diffuse large B‐cell lymphoma (DLBCL) have a significant difference in prognosis. This study aimed to identify potential hub genes, and key pathways involved in them. Methods Databases including Gene Expression Omnibus (GEO), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING were accessed to obtain potential crucial genes and key pathways associated with the GCB and ABC. Then qRT‐PCR and Western blot experiments were performed to verify the most clinically significant gene and pathway. Results Three cohort datasets from the GEO database were analyzed, including 195 GCB and 169 ABC samples. We identified 1113 differentially expressed genes (DEGs) between the GCB and ABC subtypes. The DEGs were mainly enriched in biological processes (BP). The KEGG analysis showed enrichment in cell cycle and Wnt signaling pathways. We selected the top 10 genes using the STRING database and Cytoscape software. We used 5 calculation methods of the cytoHubba plugin, and found 3 central genes (IL‐10, CD44, CCND2). CCND2 was significantly related to the prognosis of DLBCL patients. Besides, our experimental results demonstrated a significantly higher expression of CCND2 in the ABC‐type cell line than in the GCB‐type; it was proportional to the expression of key proteins in the Wnt signaling pathway. Conclusion CCND2 overexpression and Wnt pathway activation might be the main reasons for the poor prognosis of ABC‐DLBCL.